1. Field of the Invention.
This invention relates to novel methods and systems for the centrifugal separation of a liquid into its components of varying specific gravities and collection of these components, and more particularly, to a separation system and method for separating blood into its components and collecting platelet rich plasma and other blood components using disposable separation containers, input and output tubing, and source and collection syringes and using automated operation of system components (such as a centrifuge, syringe pumps, and valves) to separate a volume of blood in a disposable separation container into its components and then collect user-selected volumes and components (such as platelet rich plasma) from the container.
2. Relevant Background.
Centrifugation utilizes the principle that particles suspended in solution will assume a particular radial position within the centrifuge rotor based upon their respective densities and will therefore separate when the centrifuge is rotated at an appropriate angular velocity for an appropriate period of time. Centrifugal liquid processing systems have found applications in a wide variety of fields. For example, centrifugation is widely used in blood separation techniques to separate blood into its component parts, that is, red blood cells, platelets, white blood cells, and plasma.
The liquid portion of the blood, referred to as plasma, is a protein-salt solution in which red and white blood cells and platelets are suspended. Plasma, which is 90 percent water, constitutes about 55 percent of the total blood volume. Plasma contains albumin (the chief protein constituent), fibrinogen (responsible, in part, for the clotting of blood), globulins (including antibodies) and other clotting proteins. Plasma serves a variety of functions, from maintaining a satisfactory blood pressure and providing volume to supplying critical proteins for blood clotting and immunity. Plasma is obtained by separating the liquid portion of blood from the cells suspended therein.
Red blood cells (erythrocytes) are perhaps the most recognizable component of whole blood. Red blood cells contain hemoglobin, a complex iron-containing protein that carries oxygen throughout the body while giving blood its red color. The percentage of blood volume composed of red blood cells is called the “hematocrit.” White blood cells (leukocytes) are responsible for protecting the body from invasion by foreign substances such as bacteria, fungi and viruses. Several types of white blood cells exist for this purpose, such as granulocytes and macrophages which protect against infection by surrounding and destroying invading bacteria and viruses, and lymphocytes which aid in the immune defense. Platelets (thrombocytes) are very small cellular components of blood that help the clotting process by sticking to the lining of blood vessels. Platelets are vital to life, because they help prevent both massive blood loss resulting from trauma and blood vessel leakage that would otherwise occur in the course of normal, day-to-day activity.
If whole blood is collected and prevented from clotting by the addition of an appropriate anticoagulant, it can be centrifuged into its component parts. Centrifugation will result in the red blood cells, which weigh the most, packing to the most outer portion of the rotating container, while plasma, being the least dense will settle in the central portion of the rotating container. Separating the plasma and red blood cells is a thin white or grayish layer called the buffy coat. The buffy coat layer consists of the white blood cells and platelets, which together make up about 1 percent of the total blood volume. These blood components, discussed above, may be isolated and utilized in a wide range of diagnostic and therapeutic regimens. Various techniques and apparatus have been developed to facilitate the separation and collection of blood components. The most widely used systems are centrifugal systems, also referred to as blood-processing systems, and are usually discontinuous-flow or continuous-flow devices.
In discontinuous-flow systems, whole blood from the donor or patient flows through a conduit into the rotor or bowl where component separation takes place. These systems employ a bowl-type rotor with a relatively large (typically 200 ml or more) volume that must be filled with blood before any of the desired components can be harvested. When the bowl is full, the drawing of fresh blood is stopped, the whole blood is separated into its components by centrifugation, and the unwanted components are returned to the donor or patient through the same conduit intermittently, in batches, rather than on a continuous basis. When the return has been completed, whole blood is again drawn from the donor or patient, and a second cycle begins. This process continues until the required amount of the desired component has been collected. Discontinuous-flow systems have the advantage that the rotors are relatively small in diameter but may have the disadvantage of a relatively large extracorporeal volume (i.e., the amount of blood that is out of the donor at any given time during the process). Discontinuous-flow devices are used for the collection of platelets and/or plasma and for the concentration and washing of red blood cells. They are used to reconstitute previously frozen red blood cells and to salvage red blood cells lost intraoperatively. Because the bowls in these systems are rigid and have a fixed volume, however, it has been difficult to control the hematocrit of the final product, particularly if the amount of blood salvaged is insufficient to fill the bowl with red blood cells.
One example of a discontinuous-flow system is disclosed by McMannis, et al., in his U.S. Pat. No. 5,316,540, and is a variable volume centrifuge for separating components of a fluid medium, comprising a centrifuge that is divided into upper and lower chambers by a flexible membrane, and a flexible processing container bag positioned in the upper chamber of the centrifuge. The McMannis, et al., system varies the volume of the upper chamber by pumping a hydraulic fluid into the lower chamber, which in turn raises the membrane and squeezes the desired component out of the centrifuge. The McMannis, et al., system takes up a fairly large amount of space, and its flexible pancake-shaped rotor is awkward to handle. The McMannis, et al., system does not permit the fluid medium to flow into and out of the processing bag at the same time, nor does it permit fluid medium to be pulled out of the processing bag by suction.
In continuous-flow systems, whole blood from the donor or patient also flows through one conduit into the spinning rotor where the components are separated. The component of interest is collected and the unwanted components are returned to the donor through a second conduit on a continuous basis as more whole blood is being drawn. Because the rate of drawing and the rate of return are substantially the same, the extracorporeal volume, or the amount of blood that is out of the donor or patient at any given time in the procedure, is relatively small. These systems typically employ a belt-type rotor, which has a relatively large diameter but a relatively small (typically 100 ml or less) processing volume. Although continuous-flow systems have the advantage that the amount of blood that must be outside the donor or patient can be relatively small, they have the disadvantage that the diameter of the rotor is large. These systems are, as a consequence, large and often, are complicated to set up and use. These devices are used almost exclusively for the collection of platelets.
Continuous-flow systems are comprised of rotatable and stationary parts that are in fluid communication. Consequently, continuous-flow systems utilize either rotary seals or a J-loop. In many continuous-flow systems, rotary seals are formed by a stationary rigid low friction member contacting a moving rigid member to create a dynamic seal, and an elastomeric member that provides a resilient static seal as well as a modest closing force between the surfaces of the dynamic seal. In other systems, a pair of seal elements is provided having confronting annular fluid-tight sealing surfaces of non-corrodible material. These are maintained in a rotatable but fluid-tight relationship by axial compression of a length of elastic tubing forming one of the fluid connections to these seal elements.
One drawback present in the above-described continuous-flow systems has been their use of a rotating seal or coupling element between that portion of the system carried by the centrifuge rotor and that portion of the system that remains stationary. While such rotating seals have provided generally satisfactory performance, they have been expensive to manufacture and have added to the cost of the flow systems. Furthermore, such rotating seals introduce an additional component into the system which if defective can cause contamination of the blood being processed.
One flow system heretofore contemplated to overcome the problem of the rotating seal utilizes a rotating carriage on which a single housing is rotatably mounted. An umbilical cable extending to the housing from a stationary point imparts planetary motion to the housing and thus prevents the cable from twisting. To promote sterile processing while avoiding the disadvantages of a discontinuous-flow system within a single sealed system, a family of dual member centrifuges can be used to effect cell separation. One example of this type of centrifuge is disclosed in U.S. Pat. No. RE 29,738 to Adams entitled “Apparatus for Providing Energy Communication Between a Moving and a Stationary Terminal.” Due to the characteristics of such dual member centrifuges, it is possible to rotate a container containing a fluid, such as a unit of donated blood and to withdraw a separated fluid component, such as plasma, into a stationary container, outside of the centrifuge without using rotating seals. Such container systems utilize a J-loop and can be formed as closed, sterile transfer sets.
The Adams patent discloses a centrifuge having an outer rotatable member and an inner rotatable member. The inner member is positioned within and rotatably supported by the outer member. The outer member rotates at one rotational velocity, usually called “one omega,” and the inner rotatable member rotates at twice the rotational velocity of the outer housing or “two omega.” There is thus a one-omega difference in rotational speed of the two members. The dual member centrifuge of the Adams patent is particularly advantageous in that, as noted above, no seals are needed between the container of fluid being rotated and the non-moving component collection containers. The system of the Adams patent provides a way to process blood into components in a single, sealed, sterile system wherein whole blood from a donor can be infused into the centrifuge while the two members of the centrifuge are being rotated. However, the Adams system and the other continuous-flow systems are generally large and expensive units that are not intended to be portable. Further, they are also an order of magnitude more expensive than a standard, multi-container blood collection set.
Whole blood that is to be separated into its components is commonly collected into a flexible plastic donor bag, and the blood is centrifuged to separate it into its components through a batch process. This is done by spinning the blood bag for a period of about 10 minutes in a large refrigerated centrifuge. The main blood constituents, i.e., red blood cells, platelets and white cells, and plasma, having sedimented and formed distinct layers, are then expressed sequentially by a manual extractor in multiple satellite bags attached to the primary bag.
More recently, automated extractors have been introduced in order to facilitate the manipulation. Nevertheless, the whole process remains laborious and requires the separation to occur within a certain time frame to guarantee the quality of the blood components. This complicates the logistics, especially considering that most blood donations are performed in decentralized locations where no batch processing capabilities exist. This method has been practiced since the widespread use of the disposable plastic bags for collecting blood in the 1970's and has not evolved significantly since then. Some attempts have been made to apply haemapheresis technology in whole blood donation. This technique consists of drawing and extracting on-line one or more blood components while a donation is performed, and returning the remaining constituents to the donor. However, the complexity and costs of haemapheresis systems preclude their use by transfusion centers for routine whole blood collection.
There have been various proposals for portable, disposable, centrifugal apparatus, usually with collapsible bags, for example as in U.S. Pat. Nos. 3,737,096, or 4,303,193 to Latham, Jr., or with a rigid walled bowl as in U.S. Pat. No. 4,889,524 to Fell, et al. These devices all have a minimum fixed holding volume which requires a minimum volume usually of about 250 ml to be processed before any components can be collected. U.S. Pat. No. 5,316,540 to McMannis, et al., discloses a centrifugal processing apparatus, wherein the processing chamber is a flexible processing bag which can be deformed to fill it with biological fluid or empty it by means of a membrane which forms part of the drive unit. The bag comprises a single inlet/outlet tubing for the introduction and removal of fluids to the bag, and consequently cannot be used in a continual, on-line process. Moreover, the processing bag has a the disadvantage of having 650 milliliter capacity, which makes the McMannis, et al., device difficult to use as a blood processing device.
Hence, there remains a need for a centrifugal system for processing blood and other biological fluids that is compact and easy to use and that does not have the disadvantages of prior-art discontinuous and/or continuous flow systems. Such a system preferably would automatically separate the different components of whole blood that are differentiable in density and size, with a simple, low cost, disposable unit without the use of rotational coupling elements. Additionally, the system would be essentially self-contained and relatively inexpensive with the blood contacting set being disposable each time the whole blood has been separated.
Reference is made to the following commonly owned patent applications which are incorporated by reference herein in their entirety: U.S. Ser. No. 10/116,729, now U.S. Pat. No. 6,890,728, METHODS OF ISOLATING BLOOD COMPONENTS USING A MICROCENTRIFUGE AND USES THEREOF filed Apr. 4, 2002; U.S. Ser. No. 09/961,793, now U.S. Pat. No. 6,589,153, BLOOD CENTRIFUGE WITH EXTERIOR MOUNTED SELF-BALANCING COLLECTION CHAMBER filed Sep. 24, 2001; U.S. Ser. No. 09/832,711, now U.S. Pat. No. 6,579,219, FLEXIBLE CENTRIFUGE BAG AND METHODS OF USE filed Apr. 9, 2001; U.S. Ser. No. 09/833,230, now U.S. Pat. No. 6,610,002, METHOD FOR HANDLING BLOOD SAMPLE TO ENSURE BLOOD COMPONENTS ARE ISOLATED filed Apr. 9, 2001; U.S. Ser. No. 09/833,231, now U.S. Pat. No. 6,582,350, CENTRIFUGE CONTAINER HAVING CURVED LINEAR SHAPE filed Apr. 9, 2001; U.S. Ser. No. 09/832,729, now U.S. Pat. No. 6,942,639, AUTOLOGOUS PLATELET GEL SPRAY DELIVERY SYSTEM filed Apr. 9, 2001; U.S. Ser. No. 09/832,730, now U.S. Pat. No. 6,612,975, BLOOD CENTRIFUGE WITH AN ENHANCED INTERNAL DRIVE ASSEMBLY filed Apr. 9, 2001; U.S. Ser. No. 09/833,232, now U.S. Pat. No. 6,589,155, MINIATURIZED BLOOD CENTRIFUGE HAVING SIDE MOUNTED MOTOR WITH BELT DRIVE filed Apr. 9, 2001; U.S. Ser. No. 09/832,881, now abandoned, BLOOD CENTRIFUGE HAVING OVERHANGING DISPOSABLE BLOOD CONTAINER filed Apr. 9, 2001; U.S. Ser. No. 09/832,741, now U.S. Pat. No. 6,596,181, HARD SHELL DISPOSABLE BLOOD RESERVOIR HAVING COMPLEX INTERNAL DESIGN FOR USE IN A CENTRIFUGE filed Apr. 9, 2001; U.S. Ser. No. 09/832,516, now U.S. Pat. No. 6,605,028, BLOOD CENTRIFUGE HAVING INTEGRAL HEATING TO CONTROL CELLULAR COMPONENT TEMPERATURE filed Apr. 9, 2001; U.S. Ser. No. 09/832,463 SYSTEM AND METHOD FOR AUTOMATED SEPARATION OF BLOOD COMPONENTS filed Apr. 9, 2001, now U.S. Pat. No. 6,790,371; U.S. Ser. No. 09/833,233 BLOOD CENTRIFUGE HAVING CLAMSHELL BLOOD RESERVOIR HOLDER WITH INDEX LINE filed Apr. 9, 2001, now U.S. Pat. No. 6,835,316; U.S. Ser. No. 09/833,234 SYSTEM FOR THE PRODUCTION OF AUTOLOGOUS PLATELET GEL filed Apr. 9, 2001, now U.S. Pat. No. 6,596,180; U.S. Ser. No. 09/832,518 AUTOLOGOUS PLATELET GEL HAVING BENEFICIAL GEOMETRIC SHAPES AND METHODS OF MAKING THE SAME filed Apr. 9, 2001, now U.S. Pat. No. 6,942,880; U.S. Ser. No. 09/832,517 SYSTEM FOR THE PRODUCTION OF AUTOLOGOUS PLATELET GEL USEFUL FOR THE DELIVERY OF MEDICINAL AND GENETIC AGENTS filed Apr. 9, 2001, now U.S. Pat. No. 6,719,901.